Strains of enterotoxigenic E. coli from human cases of diarrhea were screened for their ability to hemagglutinate human group A and B and guinea pig erythrocytes in the presence of mannose at 0 degrees centigrade. These conditions allow for detection of colonization antigens (K88,K99 of animal enterotoxigenic E. coli and the colonization factor antigen (CFA) of human strain H10407). The specific hemagglutination ability of these strains is being compared to their ability to adhere to human mucosal epithelial cells and to the small bowel of infant rabbits. Toxigenic, HA positive strains are currently undergoing genetic analysis of their plsmid composition. Use of curing agents has allowed us to isolate isogenic derivatives lacking one or more plasmids found in the parental strain. These isogenic sets are being compared for their ability to: (1) produce enterotoxins, (2) cause pili specific hemagglutination of erythrocytes and (3) adhere to human mucosal epithelial cells. Using a pair of isogenic strains (334LT/ST ion HA ion and 334 LL LT ST HA) we have been able to isolate the specific HA receptor which we term specific HA pili. Examination by electron microscopy revealed the presence of an apparently homogenous para-crystalline material. This preparation was used to produce antisera against the specific HA pili or receptor. This monospecifc sera was used to screen other human toxigenic isolate for this antigen. Many of our toxigeic isolates particularly the most recent isolates, were found to react with antisera. This pili antisera will aid in clarification of the role of mannose-resistant HA pili in the specific attachment of toxigenic E. coli to the intestinal mucosa.